An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.
Characterisation Of The Role Of Mesenchymal Phenotypes And EGFR In Treatment-resistant Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$113,237.00
Summary
Phenotypic change has been identified in multiple settings relating to melanoma progression and metastasis. We have identified a degree of overlap between features of phenotypic plasticity, epithelial-to-mesenchymal transition, and the emergence of treatment resistance. This project will further examine mechanisms underlying these changes, focusing on the role of the epidermal growth factor.
Understanding Intrinsic And Acquired Resistance To Anti-FGFR Therapies
Funder
National Health and Medical Research Council
Funding Amount
$797,051.00
Summary
In vitro and in vivo preclinical data suggests that inhibition of FGFR in endometrial cancer patients may be a viable therapeutic approach. Data from other cancers suggests that despite remarkable initial responses to kinase inhibitors, cancer cells eventually develop resistance. This project aims to identify and characterize the mechanisms of resistance that emerge following FGFR inhibition in order to design combination therapies that may delay and/or prevent the emergence of resistance.
Chronic myeloid leukaemia was almost always fatal before the development of imatinib a decade ago, the first tyrosine kinase inhibitor (TKI) developed to treat a human cancer. There are now more potent TKIs that are effective in cases of resistance to imatinib. The challenge now is to optimise the achievement of remissions using these drugs and convert CML into a curable condition. This will be the focus of my NHMRC Practitioner Fellowship over the next 5 years.
The FGFR Family As Drivers And Biomarkers Of Regorafenib Response In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$670,784.00
Summary
The drug regorafenib has recently emerged as a potential new treatment for patients with gastric (stomach) cancer. We have discovered that gastric cancer cell lines which express high levels of members of the FGFR family are highly sensitive to this drug. This project will define the potential of targeting the FGFR family in gastric cancer,the value of FGFR1-4 as markers of regorafenib response, and develop strategies for enhancing regorafenib activity in this difficult to treat disease.
Colorectal cancer (CRC) is one of the most common causes of cancer-associated death in the world. We aim to understand why some CRC patients stop responding to EGFR therapy. In particular, we will study small molecules called cytokines that are produced by the tumour microenvironment and determine if the inhibition of these cytokines can over-come the acquired resistance to therapy. Our goal is to identify new ways to improve the current treatment options for CRC patients.
Defining Ubiquitin Ligase Substrates: New Therapeutic Strategies In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Current cancer therapies use drugs that target both tumor cells and rapidly growing normal cells – causing side effects and limiting effectiveness. Newer treatments aim to target molecules that are unique to tumor cells, leaving normal cells unharmed. This project will study a process that tags proteins for destruction by a cellular recycling system, which is often disrupted in cancer. This research will not only help us understand how cancer develops, but also identify new targets for therapy.
Toll-like Receptor 2 Signalling As A Potential Therapeutic Target In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$323,091.00
Summary
Stomach cancer is the fourth most deadly cancer in the world. Stomach cancer is closely linked with inflammation, and we have shown that a key inflammatory molecule, called toll-like receptor 2 (TLR2), can drive the development of stomach cancer. However, this occurs in a non-inflammatory manner. My research aims to understand how TLR2 is involved in the progression of stomach cancer, with the ultimate goal to find an early biomarker of disease, and to develop better therapies.
Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
Novel Dual Domain Targeting Strategies Against ErbB Receptors
Funder
National Health and Medical Research Council
Funding Amount
$711,216.00
Summary
This project will develop innovative strategies to treat cancer through novel antibodies to erbB growth factor receptors, and identify ways to improve conventional treatments.